中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (4): 514-517.doi: 10.4103/1673-5374.155426

• 综述:神经损伤修复保护与再生 • 上一篇    下一篇

基质相互作用调节神经营养因子介导的轴突生长和路径

  

  • 收稿日期:2015-02-14 出版日期:2015-04-22 发布日期:2015-04-22

Matrix interactions modulate neurotrophin-mediated neurite outgrowth and pathfinding

Christopher M. Madl 1, Sarah C. Heilshorn 2   

  1. 1 Department of Bioengineering, Stanford University, Stanford, CA 94305, USA
    2 Department of Materials Science and Engineering, Stanford University, Stanford, CA 94305, USA
  • Received:2015-02-14 Online:2015-04-22 Published:2015-04-22
  • Contact: Sarah C. Heilshorn, Ph.D., heilshorn@stanford.edu.
  • Supported by:

    This work was supported by the National Institutes of Health (1DP2-OD006477, R01-DK085720, R21-AR062359-01), the National Science Foundation (DMR-0846363).

摘要:

基质生物化学和神经营养因子是已知可以调节神经突生长和路径的两个因素。然而,有关这两个因素之间的相互作用研究较少。以前的研究工作已经表明,基质的生物生化特性可以改变响应于神经营养因子的神经突起生长,但细胞粘合配体浓度的重要性仍然是未知的。文章中,证明了基质结合细胞粘接性配体密度和可溶性神经生长因子的治疗在背根神经节之间对神经突生长的协同效应,这种协同作用是通过L1细胞粘附分子通过雪旺细胞神经突接触介导的。细胞粘接性配体密度显示出了可以改变响应神经生长因子梯度的背根神经节轴突的路径行为,而更多的是细胞粘接性矩阵能促进轴突生长,较弱的细胞粘接性矩阵可促进更有效的轴突路径。这些研究强调了在设计用于周围神经再生的生物材料时,同时考虑矩阵生物化学和神经营养因素的重要性。

Abstract:

Both matrix biochemistry and neurotrophic factors are known to modulate neurite outgrowth and pathfinding; however, the interplay between these two factors is less studied. While previous work has shown that the biochemical identity of the matrix can alter the outgrowth of neurites in response to neurotrophins, the importance of the concentration of cell-adhesive ligands is unknown. Using engineered elastin-like protein matrices, we recently demonstrated a synergistic effect between matrix-bound cell-adhesive ligand density and soluble nerve growth factor treatment on neurite outgrowth from dorsal root ganglia. This synergism was mediated by Schwann cell-neurite contact through L1CAM. Cell-adhesive ligand density was also shown to alter the pathfinding behavior of dorsal root ganglion neurites in response to a gradient of nerve growth factor. While more cell-adhesive matrices promoted neurite outgrowth, less cell-adhesive matrices promoted more faithful neurite pathfinding. These studies emphasize the importance of considering both matrix biochemistry and neurotrophic factors when designing biomaterials for peripheral nerve regeneration.

Key words: neurotrophic factors, cell-adhesive ligands, dorsal root ganglia, L1CAM, nerve growth factor, biomaterials, elastin-like proteins